turning the promise of synthetic biology into commercial reality...

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Turning the Turning the promisepromise of synthetic biology into of synthetic biology into commercial reality commercial reality for health and energyfor health and energy

European Comission Synthetic Biology Workshop, European Comission Synthetic Biology Workshop, 18 March 201018 March 2010

Joel R. CherryJoel R. CherrySVP, Research Programs and OperationsSVP, Research Programs and Operations

Do Not Distribute Without Prior Authorization 2

► Started in 2004 by four postdocs from UC Berkeley Professor Jay Keasling ‘s lab

► Initially funded in 2005 by a grant from the Gates Foundation to develop a lower cost, consistent supply of artemisinin

► Venture funded by leading investors; over $160MM in grants and equity financing

► Pioneering yeast technology enabling production of more than 50,000 hydrocarbon molecules

► Product portfolio - anti-malarial drug, diesel, jet fuel and a wide-range of chemicals

► Issued US patents covering diesel, jet, and lubricant products

► Marketing and distribution channels to deliver products in the United States and other global markets

Amyris Biotechnologies Inc. Amyris Biotechnologies Inc. Leading the Leading the ““next generationnext generation”” of renewable products of renewable products

Amyris Diesel Amyris Diesel precursorprecursor

Amyris Amyris engineered yeastengineered yeast

Micrograph of fermentation fluids from production of Amyris Diesel (April, 2008)


OverviewOverview

Technology Enables Broad Product OpportunitiesTechnology Enables Broad Product Opportunities

Bio-derived products

+

jet fuel 2020 estimate 124 billion gallons

> 50,000 isoprenoid

compounds

+

Amyris renewable pathway

Oil

Traditional oil source

Amyris genetically engineered yeast

malaria drug non-profit: treat over 200 million people annually

diesel2020 estimate 450 billion gallons = Petroleum products

+

Cane millSugar cane

=

Refinery

specialty chemicals: synthetic rubbers, lubricants, etc.

Bio-derived products

•Markets growing faster than GDP•Chemicals price point not directly correlated to price of crude oil•Structurally advantaged, low-cost producer


TerpeneSynthase

ADS

p450

CPR

ArtemisinicAcid

H

H

O

HO

Farnesene Synthase

A platform technology A platform technology for production of multiple productsfor production of multiple products

XXX

YYY

Anti-Malarial DrugFirst Sale 2011

Jet/Gasoline Precursors

Sucrose

OPP

IPP

OPP

FPP

IS

H3C SCoA

O

Acetyl-CoA

OH

OHCH3

HO2C

Mevalonate

Mevalonate pathway

Isoprene

Diesel and chemical precursor


Artemisinin Project

Technology for the World

HO

O

H

H

H

H

H

H

Amorphadiene Artemisinic Acid

3-Step ChemicalSynthesis

O

O

O

OO

H

HH

O

OH

HO

HOOH

OH

Glucose

Microbial Production

Artemisinin

April, 2008 - Announced partnership with sanofi-aventis for microbial artemisinin

•Nonprofit project•Lives saved due to scalable supply of inexpensive drug•$20+MM to develop a platform for isoprenoid production


Amyris process for microbe developmentAmyris process for microbe developmentEngineering cycle to increase performanceEngineering cycle to increase performance

FSFarnesene

ERG13 ERG19ERG12 IDI1 ERG20ERG13ERG10 tHMGR

Sugar ChemicalProducts

Programmed chemical conversionYeast


The heart of synthetic biology is standardizationThe heart of synthetic biology is standardization

• Tool StandardizationConsistent, simple and reliable enzyme and/or chemical treatments for the genetic manipulation of organisms

• Parts StandardizationGenetic elements that can be easily interchanged using the same or similar tools

• Process StandardizationConsistent, simple and reliable methods for the insertion and deletion of genetic elements


Aut

omat

ed S

trai

n co

nstr

uctio

n

1

2

3

Stan

dard

pra

ctic

e

1

2

3

1

2

3

Automated construction

Traditional construction

Computer assisted design

Labor intensive planning

Hand crafted construction

Robotics platform for unit operations

Relatively slow, expensive, error-prone

Fast, inexpensive,

reliable

Standardization & Automation of Strain EngineeringStandardization & Automation of Strain EngineeringRapid, reliable microbial engineeringRapid, reliable microbial engineering

1

2

3

4 4 week cycle, 40 strains per cycle

with 4 FTEs

6 week cycle, 5000 strains per cycle

with 4 FTEs

4


Automated strain engineering is a reality at AmyrisAutomated strain engineering is a reality at Amyris

Computer aided design (CAD) & RYSE

Automated rational strain engineering

HTP Screening

2 liter fermentation300 literfermentation

Production in Brazil


The first run of ASEThe first run of ASE


WHY? Automated strain engineering standardizes parts, reduces WHY? Automated strain engineering standardizes parts, reduces failure rates, decreases costs, increases strains tested.failure rates, decreases costs, increases strains tested.

Traditional strain engineering250 strains/month10 strain/biologist/month$2,400/strainFirst attempt success rate: 70%

Automated strain engineering5000 strains/month with 4 FTE’s1000 strains/biologist/month$60/strainFirst attempt success rate: 90%

ASE

2007 2008 2009 2010


The payoff: Better strains fasterThe payoff: Better strains faster


Fermentation derived hydrocarbons = lower processing costsFermentation derived hydrocarbons = lower processing costs


Production at scale: lab to pilot to commercialProduction at scale: lab to pilot to commercial

11stst barrels of Amyris Renewable Diesel from Pilot Plant, Q1 2009barrels of Amyris Renewable Diesel from Pilot Plant, Q1 2009

Production at 60,000 L scale, Q2 2009

Demo Plant Fermenter, Campinas Brazil Q2 2009Demo Plant Fermenter, Campinas Brazil Q2 2009


Products Products –– Renewable Fuels and ChemicalsRenewable Fuels and ChemicalsDiesel fuel registered with the EPA at a 20% blendDiesel fuel registered with the EPA at a 20% blend

Note: Amyris diesel will be used in blends with conventional fuels; values shown for Amyris diesel is for our biomass derived blending component; SME = Soy Methyl Esters

+1

< – 50 Amyris

SME

# 2-D

47

58.1

40-55

Cetane Number

Amyris

SME

# 2-D

Energy Density1000 BTU/gal

118

121

115-142

Amyris

SME

# 2-D

0 50 100 1500 20 40 60-75 -50 -25 0

-9 to-30

Cloud Pointdegrees Celsius

Additional benefits of Amyris renewable diesel compared to #2-Diesel•90%+ lower greenhouse gas emissions•No sulfur•produces lower NOx and particulate emissions


Participation in the value chainParticipation in the value chain

Amyris will participate in various aspects along the biofuels value chain

Amyris GreenLaneTM

Partner with large scale manufacturer with access

to low cost feedstocks

Partner with large scale manufacturer with access

to low cost feedstocks

• Take product from plant gate to wholesaler

• Logistics contracts to facilitate high volume

distribution

• Take product from plant gate to wholesaler

• Logistics contracts to facilitate high volume

distribution

• Sell to fastest growing retail segment

• Access to end customers (commercial

accounts)

• Sell to fastest growing retail segment

• Access to end customers (commercial

accounts)

Commercial Commercial CustomersCustomers

ManufacturingManufacturingProductProduct

Transportation Transportation & Logistics& Logistics

Terminal &Terminal &blend racksblend racks

Retail Customers

TechnologyTechnologyFeedstock

Build production platform from distressed assets

Build production platform from distressed assets


Critical path to 2011 Critical path to 2011 –– commercial plant in Brazilcommercial plant in Brazil

SuggestedSite

EthanolDistillation

EthanolFermentation Cane Mill

Juice ClarificationPre-Evaporation

Suggested site (recent)


Begin mill conversion to produce Amyris renewable products• Engineering of commercial plant has been finalized and EPCM has been engaged

First large scale production of Amyris renewable products

Continue mill conversion and expansion

First commercial production by third party mills under “capital light” strategy

20092009 20102010 20112011 20122012

R&D center inaugurated in 2008 in Campinas

Q2: Pilot plant operational; Demo Facility opened

Q4: Acquire EtOH Mills • Ongoing operations

provide immediate revenue and cash flow

Plan to commercial production Plan to commercial production –– timeline timeline


TakeTake--homehome messagesmessages

• Standardization of parts, tools and processes has facilitated automated strain engineering

• ASE is game changing for the development of renewables

• Amyris is on track for 2011 commercial production of diesel and chemical products


Thanks for listeningThanks for listening


Disclaimer

This paper was produced for a meeting organized by Health & Consumers DG and represents the views of its author on the subject. These views have not been adopted or in any way approved by the Commission and should not be relied upon as a statement of the Commission's or Health & Consumers DG's views. The European Commission does not guarantee the accuracy of the data included in this paper, nor does it accept responsibility for any use made thereof.

turning the promise of synthetic biology into commercial reality...

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